Systemic lupus erythematosus (SLE) is an autoimmune condition more commonly observed in women of childbearing age. The most commonly reported initial presentations were fatigue, arthritis, and skin manifestations. However, due to the involvement of a variety of organs, diagnosis remains a challenge for physicians. Our patient is a 48-year-old lady who presented with severe bilateral lower extremity edema with non-resolving right lower lobe pneumonia and ipsilateral exudative pleural effusion. Her leg swelling was not responding to diuretics, and her pneumonia was not improving following a course of antibiotics. This unusual presentation prompted an autoimmune workup, which later revealed a diagnosis of SLE with class 5 lupus nephritis. Pleuritis, exudative pleural effusion, and lupus nephritis have been associated with autoimmune disorders in the literature, but this is an uncommon initial presentation in SLE without other clinical manifestations. Our case report highlights the challenges in the diagnosis of an atypical case of SLE and the need to maintain high clinical suspicion for SLE, especially in female patients with multiorgan involvement.

UNASSIGNED: To determine the full range of ophthalmological clinical manifestations in systemic lupus erythematosus (SLE) and to compare the systemic features associated with them.
UNASSIGNED: Files of 13 patients with ocular SLE (n = 20 eyes) diagnosed as per the American College of Rheumatology (ACR) 2012 revised criteria were retrospectively reviewed.
UNASSIGNED: The following clinical manifestations were found: keratoconjunctivitis sicca (n = three patients), anterior uveitis associated with an inflammatory pseudo-tumor orbital mass (n = one patient, one eye), episcleritis and periorbital edema (n = one patient, two eyes), posterior scleritis (n = one patient, two eyes), bilateral papillary edema in the context of idiopathic intracranial hypertension (n = one patient, one eye), inflammatory optic neuritis (n = one patient, one eye), and lupus retinopathies with varying degrees of capillary occlusions mainly arteriolar (n = seven patients, 13 eyes) and larger arteries or veins (retinal arteries occlusions and retinal veins occlusions) (n = one patient, two eyes). Some patients presented with combined ophthalmological manifestations.Systemic SLE was discovered by its ophthalmic manifestation in three cases (23%) and was previously known in the other 10 cases (77%). On average, ocular symptoms were seen 8 years after the initial diagnosis of SLE. Other systemic SLE disorders included cutaneous disorders (77%), joint disorders (38%), central nervous system (CNS) disorders (23%), renal disorders (38%), and oral ulcers (23%).Treatment of the ophthalmic system manifestations of lupus included local steroid therapies along with systemic immunosuppression.The most common laboratory ACR criteria were: high levels of antinuclear antibodies (ANA) (100%), positive anti-Sm (64%), anti-dsDNA (27%), low complement levels (27%), and positive antiphospholipid (APL) antibodies (18%).
UNASSIGNED: SLE activity in the ophthalmic system is characterized by its functional severity and the range of involvement can be categorized by anatomical involvement: presence of anterior uveitis, episcleritis, scleritis, periorbital edema, posterior uveitis with retinal vascular ischemia, or papillary edema. Not currently part of the diagnosis criteria of the SLE ACR given its rarity, the ocular localization of the pathology led to the diagnosis of SLE in three cases; thus, developing a greater understanding of ocular lupus may help in identifying and treating systemic manifestations of lupus earlier.

The cyclic GMP-AMP synthase (cGAS), a prominent intracellular DNA sensor in mammalian cells, controls the innate immune response and the stimulator of interferon genes (STING)-mediated synthesis of pro-inflammatory cytokines, such as type-I interferon (IFN-I). For decades, IFN-I has been hypothesized to be essential in the development of systemic lupus erythematosus (SLE), a chronic multisystem autoimmunity characterized by immune complex (IC) deposition in small vessels. Recent findings revealed that the activation of the cGAS-STING pathway by self-DNA would propagate the autoimmune responses via upregulating IFN-I production in SLE. In this review, we aimed to provide a comprehensive outlook of the role of the cGAS-STING pathway in SLE pathobiology, as well as, a better understanding of current therapeutic opportunities targeting this axis.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients.
METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index.
RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97).
CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

UNASSIGNED: The coronavirus disease 2019 (COVID-19) pandemic has limited healthcare delivery for patients with chronic diseases, including Systemic Lupus Erythematosus (SLE). This study aims to describe the outcomes of patients with SLE in a national COVID-19 referral center in the Philippines.
UNASSIGNED: A review of records of all adult patients with SLE seen in the University of the Philippines-Philippine General Hospital (UP-PGH) from March 2020 to December 2021 was done. Data about patient characteristics, health encounters, and outcomes before and after the first visit during the study period were extracted. Descriptive statistics were employed.
UNASSIGNED: Our population of 403 patients was predominantly young (mean age 34.53 ± 11.14 years), female, and unemployed. This consisted of 370 known cases of SLE, 92 were diagnosed in institutions outside UP-PGH, and 33 new patients. Over the 22-month study period, there were 2,093 medical encounters, most of which were teleconsultations (81.70%). During an average gap of 53.6 ± 26.7 weeks between the last consultation and the first visit within the pandemic study period, 84 patients (22.70%) discontinued at least one of their SLE control medications, 68 (18.38%) patients developed a lupus flare, and 79 (21.35%) were hospitalized for various reasons. On their return to the rheumatology clinic during the pandemic, 37.47% were in lupus flare, 28.29% needed to be hospitalized, and 20 died. However, 86.75% of flares were controlled. During subsequent health encounters, 48 patients had a new flare (43 of these were controlled) and 20 died. The most common reason for hospitalization (n=160) was lupus disease flare and the most common cause of death (n=40) was pneumonia. Sixty patients acquired COVID-19 infection from which most recovered and four died.
UNASSIGNED: Audio teleconsultation was the most common method used by our lupus cohort to interact with their doctors during the pandemic. There was an average of a year-long interruption in medical care for 62.70%. More than a third developed a disease flare and 15% acquired COVID-19 but outcomes were good in more than 85%. Despite the challenges posed by the pandemic, the majority of our lupus cohort who were able to continue their treatment had favorable outcomes.

UNASSIGNED: Systemic Lupus Erythematosus (SLE) can have an insidious onset and a fatal prognosis in children. Patients presenting without typical signs of SLE should undergo further evaluation if they are not responding to the initial diagnosis and treatment. This is especially true for patients with rapidly progressing symptoms and deterioration in spite of treatment.
UNASSIGNED: Pediatric Systemic Lupus Erythematosus is a chronic autoimmune disorder with various organ involvement pulmonary involvement in the course of this disorder is a rare yet potentially life-threatening complication. In this case report we highlight the findings of a 16-year-old girl acutely and initially presenting with cough and fever, eventually complicating to diffuse alveolar hemorrhage and gradual loss of consciousness. Although the patient was started on immunosuppressive treatment after the diagnosis of lupus, based on renal and hematological impairment, was made and initially responded, she eventually deteriorated.

BACKGROUND: A symmetric leukoencephalopathy can occur in the context of systemic lupus erythematosus (SLE), often as a first manifestation of underlying rheumatologic disease. Recognition of this distinctive syndrome can prompt investigation for SLE when undiagnosed, or prompt treatment initiation when the diagnosis is already known. Earlier recognition of this syndrome could lead to more effective treatment of the disease.
METHODS: Clinical, laboratory, and radiographic features of three patients were described from an academic medical center in the United States with treatment dates between 2015 and 2022. A systematic review of literature from 1991 to 2023 yielded data for an additional 23 patients.
RESULTS: Twenty-six total patients with symmetric leukoencephalopathy were included in this study. The median age of the patients was 37 years (range 10-69), 22 patients (85 %) were female, and 4 (15 %) were male. Fourteen of 26 patients (54 %) had this as the first clinical manifestation of SLE. Contrast enhancement was present on MRI brain in 3/26 (88 %) patients. Twenty patients (77 %) were treated with pulse-dose steroids, and all but one patient received some immunomodulatory therapy. Seven patients (27 %) progressed to death. No meaningful predictive differences were found between patients who survived and those who did not.
CONCLUSIONS: In this case series and literature review patients developed symmetric leukoencephalopathy in systemic lupus erythematosus most often as the first clinical manifestation of SLE. Clinicians should consider this syndrome in any patient with acute onset of symmetric leukoencephalopathy on brain magnetic resonance imaging.

Protein kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ-deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement for PKCδ in preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ acts as a key regulator of B cell tolerance by selectively deleting anti-dsDNA B cells in the germinal center (GC). PKCδ\'s tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ\'s tolerance activity and discuss the potential significance of therapeutically targeting PKCδ\'s tolerance activity in the GC for selectively inhibiting lupus autoimmunity.

This study sought to compare in vivo sex differences in either a Th1-dominant CTL response or a Tfh-mediated lupus-like antibody response using the parent-into F1 murine model of acute or chronic GVHD respectively. In acute GVHD we observed no significant sex differences in the hierarchy of donor CD8 CTL elimination of splenocyte subsets. B cells were the most sensitive to elimination in both sexes; however, the male response was significantly stronger. Sex differences in chronic GVHD were more widespread; females exhibited significantly greater numbers of total splenocytes and host CD4 Tfh cells, B cells and CD8 T cells consistent with reports of greater female autoantibody production in this model. The more potent male CTL response in acute GVHD conflicts with reports of greater female CTL responses following infections or vaccines and may reflect the absence of exogenous innate immune stimuli in this model.

Thiamine is an essential water-soluble vitamin that must be obtained through diet. This vitamin is crucial for various biochemical reactions and is vital for aerobic metabolism. When individuals are deficient in thiamine, which can be due to hypermetabolism (such as in inflammation, ischemia, or malnutrition, among other reasons), anaerobic metabolism may be utilized to maintain energy needs. Such chemical processes produce lactic acid. Excess lactic acid can cause various clinical signs and symptoms, though lactate dehydrogenase (LDH) can typically break down this compound. The following case presents a very unusual instance where a 51-year-old Caucasian woman presented with the chief complaint of ongoing and severe abdominal pain. After an extensive work-up ruling out numerous diagnoses and an eight-day hospital stay, it was believed that she may be suffering from hyperlactatemia secondary to thiamine deficiency, as she improved significantly after administration of this vitamin. It was thought that this was likely due to her previous systemic lupus erythematosus (SLE) diagnosis, vasculitis, chronic inflammation, and a hypermetabolic state, in addition to concurrent LDH malfunction.